The fundamental chromophore of the chlorophylls is a chlorin, which differs from a porphyrin in having one pyrrole ring reduced at the β-positions (Chart 1).
In addition, chlorophylls contain an annulated cyclopentyl ring bearing a 131-oxo group (known as the isocyclic ring) at the periphery of the macrocycle (Scheer, H. In Chlorophylls; Scheer, H. Ed.; CRC Press, Inc.: Boca Raton, Fla., USA, 1991; pp 3-30). Chlorophyll a exhibits a strong B band at 430 nm and a strong Qy band at 662 nm (FIG. 3).
The 131-oxo group, which is conjugated with the π-electron of the macrocycle, causes a significant redshift of the long wavelength absorption band (Qy band) and increases the intensity of the Qy band compared to synthetic chlorins lacking a 131-oxo substituent. That the hyperchromic and bathochromic effects stem from the keto group and not the annulated cyclopentanyl ring alone has been proved by direct comparison of chlorophyll analogues (Chart 2). Indeed, a nickel pyropheophorbide (NiMPPh) absorbs at 638 nm (ε˜50,000 M−1 cm−1) whereas the deoxo analogue (NiDMPPh) absorbs at 608 nm (ε˜25,000 M−1cm−1) (Boldt, N. J et al., J. Am. Chem. Soc. 1987, 109, 2284-2298).

The design and synthesis of molecules with intense absorption in the red or near-IR regions enables a variety of applications encompassing solar cells (Linke-Schaetzel, M. et al., Thin Solid Films 2004, 451, 16-21), medical imaging (Licha, K. Top. Curr. Chem. 2002, 222, 1-29) and photodynamic therapy (Pandey, R. K.; Zheng, G. In The Porphyrin Handbook; Kadish, K. M.; Smith, K. M.; Guilard, R., Eds.; Academic Press: San Diego, 2000; Vol. 6, pp. 157-230). The ability to install the isocyclic ring in hydroporphyrins (chlorins and bacteriochlorins) is of considerable interest, given the beneficial spectral effects of the conjugated keto group. In addition, the keto group is expected to shift the oxidation potential to more positive values, thereby stabilizing the macrocycle to oxidation. However, only a few routes are known for the construction of the isocyclic ring (Scheme 1).

A review of synthetic manipulations of chlorophyll compounds is available (Pavlov, V. Y.; Ponomarev, G. V. Chemistry of Heterocyclic Compounds 2004, 40, 393-425). Fischer reported the dehydration of a (hydroxymethylcarbonyl)porphyrin using conc. H2SO4 to give the “pheoporphyrin” bearing the isocyclic ring (A→B)(Fischer, H.; Laubereau, O. Justus Liebigs Ann. Chem. 1938, 535, 17-37), and Dieckmann cyclization to convert chlorin e6 trimethyl ester to methyl pheophorbide a (C→D) (Fischer, H.; Oestreicher, A. Justus Liebigs Ann. Chem. 1941, 546, 49-59). The Dieckmann cyclization initially was carried out using KOH/pyridine or sodium methoxide in methanol/acetone, but since then has been performed with milder bases such as potassium tert-butoxide/pyridine (Smith, K. M. et al., Bioorg. Chem. 1980, 9, 1-26; Smith, K. M. et al., J. Am. Chem. Soc. 1980, 102, 2437-2448; J. Org. Chem. 1980, 45, 2218-2224), sodium bis(trimethylsilylamide)(Gerlach, B.; Brantley, S.; Smith, K. M. J. Org. Chem. 1998, 63, 2314-2320), or potassium tert-butoxide/collidine (Pallenberg, A. J.; Dobhal, M. P.; Pandey, R. K. Org. Process Res. Dev. 2004, 8, 287-290). Kenner employed the oxidative cyclization of a β-ketoester at the 13-position of a porphyrin to give the pheoporphyrin (Cox, M. T. et al., J. Am. Chem. Soc. 1969, 91, 1232-1233; Kenner, G. W. et al., J. Chem. Soc. Chem. Comm. 1972, 844-845; Cox, M. T. et al., J. Chem. Soc. Perkin Trans. I 1974, 512-516; Kenner, G. W. et al., J. Chem. Soc. Perkin Trans. I 1974, 527-530), which Smith extended to conversion of a chlorin to the methyl pheophorbide a (E→F)(Smith, K. M.; Lewis, W. M. Tetrahedron 1981, 37 Supp. 1, 399-403). Finally, a dipyrromethane bearing an annulated cyclopentane ring (G) has provided an intriguing route to deoxophylloerythroetioporphyrin (H), although this macrocycle does not contain the desired 131-oxo functionality (Flaugh, M. E.; Rapoport, H. J. Am. Chem. Soc. 1968, 90, 6877-6879; Li, W.; Lash, T. D. Tetrahedron Lett. 1998, 39, 8571-8574; Lash, T. D.; Catarello, J. J. Tetrahedron 1993, 49, 4159-4172). Each of these routes has certain attractions; however, none appeared compatible with our existing synthetic route to chlorins.